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Saturday, 24 October 2015

LadderDNA

DNA was famously discovered in 1869 by Friedrich Miescher, just ten years after Darwin published the Origin of Species. But it wasn't until 1952 that it was demonstrated to be the the key to heredity (in the T2 phage), and then its structure and modus operandi were deduced a year later.

In retrospect, its helical structure might have been anticipated (easy for me to say with hindsight, of course...). If you take any random shape and stack repeated copies of it, the result is a helix. The reason is that the top face of the shape will be a fixed distance from the bottom, and at a fixed angle to it. Repeatedly copying something through a fixed distance and turning it through a fixed angle always gives a helix.

However, that helix must be very inconvenient for cells, as anyone who has had to deal with a tangle of string knows. As DNA is copied it unzips down the middle then zips itself back up again a bit downstream. Meanwhile the copy twists away forming a new chain. My late colleague Bill Whish once worked out that the molecule has to spin at 8,000 RPM while it is doing this to get the job done in time. Think of your car engine spinning at that speed and spewing out a twisted strip as it did so. Now present yourself with the problem of stopping that strip from getting hopelessly knotted up, and also not tangled with its parent DNA. It's fortunate that all this is happening in an extremely viscous medium - water. At the molecular scale water is like very thick treacle indeed. Our intuition from the engine and strip analogy is led astray by our instinct for flexibility, mass and inertia at human scales. Down with the DNA inertia is negligible, and everything stays where it is put.

But what if DNA were not a helix, but were as straight as a ladder? Many of these problems would go away. It should not be too difficult to devise a molecular ladder where that angle between one rung and the next has zero twist. If in no other way, it could be achieved by taking a twist and bonding it to its other stereo-isomer with the opposite twist to form a single rung.

The ribosome would have to be re-engineered to accommodate straight, rather than twisted, transfer RNA. But people have already made artificial ribosomes that do things like working with four-base codons (all natural ribosomes work with three-base codons) so that should not be too difficult. The actual codon to amino-acid to protein coding could remain unaltered, at the start at least.

We would then have synthetic cells that might be able to reproduce much more quickly than natural ones, or work at much higher temperatures.

And the ladder DNA would be much easier to organise in two-dimensional sheets or three-dimensional blocks. We could then try to do parallel copying of the DNA rather than the serial copying that happens at the moment - a ladder-DNA sheet could make a copy by stamping it out, rather as a printing press stamps out a page. That should speed up reproduction even further, and a similar parallelisation could be attempted with the ribosome, making proteins all in one go, as opposed to chaining them together one amino acid at a time.